The cardiac glycosides are the main pharmacologic tools in the treatment of congestive heart failure. Increasing the plasma (K ion)prior to glycoside administration protects against the life threatening arrythmias which often occur with drug overdose. Increasing plasma (Ca 2 ion) or decreasing the plasma pH increases the likelihood of cardiotoxic side effects. One objective of this project is to investigate the interactions of K ion, Ca2 ion, pH and the cardiac glycosides. With the microelectrode voltage clamp method, analysis of the slow repolarization and pacing currents as well as the steady state current voltage relation of the purkinje fibre can be achieved. From these experimental results it should be possible to formulate a model relating these clinically important ionic interactions and perhaps uncover the mechanism of their interaction. A second objective of this project is to pursue the investigation of the mechanism by which salicylates reverse and prevent the toxic electrophysiologic effects of the cardiac glycosides. Should this pursuit be successful a preventive as well as acute treatment for glycoside toxicity is within the range of possibility. A third objective of this proposal is to study the effects of ions and surface charge agents in order to learn more about the contribution of the Na-K ions exchange pump to the normal functioning of cardiac muscle.